Ruminant feedstock dietary supplement

ABSTRACT

This invention provides a control release formulation or rumen-bypass dietary supplement in compacted form. The formulation or supplement has the capability to transport fatty acid calcium salt and between about 1-75 percent of one or more rumen-protected undegraded biologically active agents to the post-ruminal digestive system of a ruminant. A feedstock containing the formulation or supplement for ruminants beneficially improves feed efficiency and body growth. The feedstock also is adapted to improve the lactational performance of dairy cattle.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a continuation-in-part of currently pendingU.S. Ser. No. 11/473,880 filed Jun. 23, 2006 entitled, “RuminantFeedstock Dietary Supplement”, which is incorporated herein byreference.

FIELD OF THE INVENTION

This invention generally relates to a control release formulation thatis supplemented with a rumen-bypass protected biologically activecontent. More specifically, in preferred embodiments this inventionrelates to ruminant feedstocks for domesticated ruminants which arecapable of delivering undegraded essential aminoacids such as lysine andmethionine to the post-rumen digestive system of ruminants such as dairycattle.

BACKGROUND OF THE INVENTION

Publications cited in the present specification are incorporated byreference.

When a feedstock for ruminants has a content of biologically activeconstituent, a substantial amount of the said constituent (e.g.,protein, aminoacids, and the like) is degraded to ammonia or carbondioxide gas by microorganisms in the rumen. This prevents effectiveutilization of the administered biologically active constituent in thefeedstock.

When special nutrients or medicaments are administered to ruminants, itis essential to protect these ingredients from decomposition in therumen. The objective is to pass the said ingredients through the rumento the omasum, and subsequently to the abomasum and absorption by thesmall intestine.

There are ongoing research and development activities which are seekingto achieve ruminant feedstock supplements which have the desiredrumen-bypass properties. Rumen-bypass formulations are reported innumerous publications such as U.S. Pat. Nos. 4,842,863; 4,948,589;5,023,091; 5,064,665; 5,093,128; 5,571,527; 5,633,004; 5,635,198;6,203,829 and 6,306,427. There is further disclosure in WO2004/080197-A2(PCT) and references cited therein.

Special effort has been directed to achieving rumen-bypass protectionfor essential aminoacids which supplement feedstocks for milk-producingruminants.

It is known that lysine and methionine are important for milk productionin dairy cattle. Journal of Dairy Science, 70, 789 (1987) reports thatrumen-protected lysine increased feed intake, milk yield and 4%fat-corrected milk production in dairy cows; rumen-protected methionineand lysine increased production of milk protein in dairy cows.

Similar results are reported in Journal of Dairy Science, 72, 1484(1989); 72, 1800 (1989); 73, 135 (1990); and 74, 2997 (1991). Data alsoindicated that added fat increased the percentage and yield oflong-chain fatty acids in cow milk. Adding ruminally-protectedaminoacids to fat-supplemented diets appeared to alleviate the milkprotein depression observed with added lipids in feedstock.

Because of the significant economic consequences of rumen-bypassundegraded dietary nutrient transport, there is continuing interest inthe development of superior rumen-bypass feedstock supplements topromote these prospective advantages.

Accordingly, it is an object of this invention to provide ruminantfeedstocks which are supplemented with a rumen-protected biologicallyactive content for advancing ruminant husbandry and for providing valueadded meat and dairy products for human consumption.

It is another object of this invention to provide rumen-bypass dietarysupplements to stabilize and maintain the health of ruminants, and toimprove the lactational performances of dairy ruminants.

It is yet another object of this invention to provide rumen-bypassdietary supplements which deliver post-rumen undegraded aminoacids inmilk-producing dairy cattle for increased milk yield and increasedproduction of milk protein.

It is a further object of this invention to provide an efficient processfor producing a rumen-bypass dietary supplement in compacted particulateform, which supplement has the capability of passing between about 20-99percent of its rumen-protected biologically active content to thepost-rumen digestive system of ruminants.

Other objects and advantages of the present invention shall becomeapparent from the accompanying description and example data.

SUMMARY OF THE INVENTION

The present invention discloses a control release formulation (e.g., arumen-bypass dietary supplement) in compacted form. In one embodiment,the control release formulation (or supplement) has the capability totransport a fatty acid salt (e.g., a fatty acid calcium salt) and one ormore rumen-protected undegraded biologically active agents (e.g., anaminoacid) to the post-ruminal digestive system of a ruminant. Inaccordance with the present invention, the rumen-bypass dietarysupplement comprises: (a) a fatty acid salt; (b) one or morebiologically active agents; (c) a free alkali metal salt and/or a freealkaline earth metal salt; and (d) a binder. In one embodiment, underruminant feeding conditions the dietary supplement has the capability totransport between about 20-99 percent of one or more rumen-protectedundegraded biologically active agents (e.g., an aminoacid) to thepost-rumen digestive system of a ruminant.

In another embodiment, the present invention provides a process forproducing a rumen-bypass dietary supplement comprising: (1) blending afatty acid salt (e.g., an alkaline earth metal salt) and one or morebiologically active agents to form solid central core particles; (2)compacting the core particles to form pellets; (3) optionally coatingthe pellets with a liquid carboxylate salt-forming fatty acidconstituent and/or a liquid carboxylate salt; and (4) optionallyapplying one or more additional coatings to the pellets with aconstituent comprising a basic inorganic alkaline earth metal compoundto create an in situ reactive carboxylate salt-forming matrix.

DETAILED DESCRIPTION OF THE INVENTION

One or more objects of the present invention are accomplished by theprovision of a control release formulation (e.g., a rumen-bypass dietarysupplement) in compacted form comprising:

(a) a fatty acid salt, for example, a C₄-C₂₄ fatty acid alkaline earthmetal salt;

(b) one or more biologically active agents, for example, an amino acid,vitamin, mineral, trace elements, enzyme, protein, non-protein nitrogencompound, medicaments, or mixtures thereof;

(c) a free alkali, for example, hydroxide and/or carbonates of alkalimetals, and/or alkaline earth metals;

(d) a binder, for example, a C₄-C₂₄ fatty acid carboxylate-salt formingconstituent; and

(e) optionally one or more additional coatings.

Other constituents may be included in the compacted formulationincluding, but not limited to, inorganic acidic salts, clays and otherinorganic and organic-based compounds, either dispersed throughout orapplied to the exterior of the compacted materials.

In one embodiment, the control release formulation of the presentinvention can be in compacted particulate form wherein the particleshave average dimensions between about 2-5 millimeters, and a densitybetween about 1-1.3 grams per cubic centimeter. In another embodiment,under ruminant feeding conditions control release formulation of thepresent invention has the capability to transport between 20-99 percentof one or more rumen-protected undegraded biologically active agents(e.g., an aminoacid) to the post-rumen digestive system of a ruminant.

Standard procedures and equipment are employed to blend ingredients,compact ingredients, and apply coatings as appropriate. Granules orpellets are coated by conventional means such as pan coating, fluidizedcoating, centrifugal fluidized coating, and the like.

A present invention dietary supplement can be in the form of spherical,elliptical or cylindrical pellets which are in compacted form.Production of compressed solids can be facilitated with commerciallyavailable pellet mills and extruders, supplied by companies such asSprout-Matador (Muncy, Pa.) and Roskamp Champion (Waterloo, Iowa).

In a preferred embodiment this invention provides a rumen-bypass dietarysupplement in compacted particulate form comprising:

(a) between about 50-90 weight percent of C₄-C₂₄ fatty acid alkalineearth metal salt;

(b) between about 5-50 weight percent of one or more biologically activeagents;

(c) between about 0.2-5 weight percent of a free alkali salt and/or analkaline earth metal salt; and

(d) between about 0.5-20 weight percent of a C₄-C₂₄ fatty acidcarboxylate-salt forming fatty acid; and

(e) optionally one or more coatings.

The central core of a typical control release formulation or dietarysupplement particle (e.g., in pellet form) comprises a blend of one ormore biological active agents (e.g., an aminoacid), a fatty acid salt(e.g., a fatty acid calcium and/or magnesium salt), a free alkali metalsalt and/or an alkaline earth metal salt and a binder. In an optionalembodiment, of the present invention, one or more additional or externalcoatings can be applied to the central core of the control releaseformulation. For example, a liquid fatty acid coating can be applied tothe surface of the central core, and the separate application of a basicinorganic reagent such as calcium hydroxide can be added to the samecentral core surface. Either coating can be applied first and the liquidfatty acid and the basic inorganic reagent may be combined together toform the reactive matrix for subsequent application on the surface ofthe pellet. The super-imposed coatings may constitute a reactive matrix,and the in-situ matrix can transform into an interlocking network ofmulti-valent fatty acid salts. The resultant periphery of the pelletstructure is a bonded hard lamina which imparts superior rumen-bypassproperties to an invention dietary supplement for incorporation inruminant feedstocks. In addition, the liquid fatty acid and the basicinorganic reagent may be combined together to form the reactive matrixfor subsequent application on the surface of the pellet.

As another optional modification, the hereinabove described central coreof a typical control release formulation or dietary supplement particle(e.g., in pellet form) can be encapsulated with an outer coating foradditional rumen-bypass capability. Suitable coating substrates includewaxes and polymers which can form a continuous film that functions as asemi-permeable barrier to a ruminal medium. This type of coatingsubsequently is capable of being at least partially disintegrated in thestrongly acidic condition of the gastric fluid in the abomasum ofruminants.

Useful coating materials include carnauba wax, beeswax,polyvinylpyrrolidone, polyacrylamide, poly(styrene/2-vinylpyridine),polyvinyl acetate, shellac, zein, benzylaminomethylcellulose,ethylcellulose, cellulose acetate, and the like, and coating materialsdisclosed in U.S. Pat. Nos. 4,194,013; 4,384,004; 4,887,621; and4,996,067.

The control release formulation of the present invention comprises afatty acid salt. In one embodiment, the fatty acid salt can be a C₄-C₂₄fatty acid calcium and/or magnesium salt. The fatty acid salt of thecontrol release formulation of the present invention may comprise fromabout 25 to about 99 weight percent, from about 50 to about 90 weightpercent, or from about 60 to about 75 weight percent, of a fatty acidsalt. In another embodiment, the fatty acid salt can be C₁₂-C₂₂ fattyacid calcium and/or magnesium salt.

The control release formulation of the present invention comprises oneor more biologically active agents. The one or more biologically activeagents of the control release formulation may comprise from about 1 toabout 75 weight percent, from 5 to about 50 weight percent, or fromabout 10 to about 40 weight percent, of one or more biologically activeagents. In one embodiment, one or more biologically active agents can beone or more amino acids, vitamins, minerals, trace elements, enzymes,proteins, non-protein nitrogen compounds, medicaments, or mixturesthereof.

When the one or more biologically active agents is an aminoacid, theessential aminoacids are of special interest. Preferred aminoacidsinclude alanine, glycine, lysine, methionine, methionine hydroxy analog,tryptophan, arginine, threonine, valine, leucine, isoleucine, histidine,phenylalanine, glutamine and glutamic acid.

For lactating dairy cattle feedstocks, a preferred control releaseformulation or dietary supplement is one that delivers high levels ofpost-rumen contents of C₁₂-C₂₂ fatty acids and one or more of lysine,methionine, methionine hydroxy analog and tryptophan.

In one embodiment, the control release formulation (e.g., a dietarysupplement) of the present invention can have a varied combination ofbiologically active ingredients, for example, the formulation maycontain from about 1-75 weight percent of an aminoacid and/or from about0.1-30 weight percent of one or more active ingredients selected fromvitamins, trace elements, proteins, non-protein nitrogen compounds,medicaments, enzymes, inorganic acidic salts, clays, and the like.

Vitamins either singly or in combination include thiamine HCl,riboflavin, pyridoxine HCl, niacin, biotin, folic acid, ascorbic acid,vitamin B₁₂, vitamin A acetate, vitamin K, vitamin D, vitamin E, and thelike.

Trace elements include compounds of cobalt, copper, manganese, iron,zinc, tin, iodine, vanadium, selenium, and the like.

Protein ingredients are obtained from sources such as dried blood ormeat meal, cottonseed meal, soy meal, dehydrated alfalfa, dried andsterilized animal and poultry manure, fish meal, powdered eggs, canolameal, and the like.

Protein equivalent ingredients include urea, biuret, ammonium phosphate,and the like.

Medicament ingredients either singly or in combination include promazinehydrochloride, chlorotetracycline, sulfamethazine, monensin, poloxalene,and the like. Oxytetracycline is a preferred antibiotic for cattleprophylaxis.

Enzymes of choice include lipolytic proteins which aid feeddigestibility, e.g., by hydrolysis of fatty acid glycerides to freefatty acid and glycerol.

As illustrated in the Examples, this invention further provides aprocess for producing the range of rumen-bypass dietary supplementsdescribed hereinabove.

As disclosed hereinabove, the core compacted particle comprises a blendof one or more biologically active agents (e.g., an amino acid) and afatty acid salt (e.g., a calcium and/or magnesium salt). The inventorshave surprisingly found that by using a binder or reactant in theformation of the core compacted particle, superior rumen-bypass can beachieved. As such, in one embodiment, the use of a binder or reactantcan be used in the process for producing the control release formulation(or the rumen-bypass dietary supplement) of the present invention. Thebinder can be, but is not limited to, a carboxylate salt-forming C₄-C₂₄fatty acids. In the practice of this embodiment, an excess of freealkali is typically used in the formation of the fatty acid calciumand/or magnesium salt. The free alkali can be a hydroxide and/orcarbonate of an alkali metal salt or alkaline earth metal salt (e.g.,Ca(OH)₂ or Mg(OH)₂). Typically, the free alkali comprises from about 0.2to about 10 weight percent of the total weight of the fatty acid salt.In another embodiment, the free alkali content is between about 0.2 andabout 5 weight percent, or from about 0.2 to about 2 weight percent, ofthe total weight of the fatty acid salt used. While not wishing to bebound by theory, it is believed that by using an excess of a free alkali(e.g., Ca(OH)₂ or Mg(OH)₂), the excess free alkali (e.g., Ca(OH)₂ orMg(OH)₂) is available for reaction, and can act as a reactant andinteract with the binder or reactant in-situ to form a fatty acid saltencapsulate in and throughout the pellet (e.g., a Ca- or Mg-fatty acidsalt encapsulate). Other sources of OH, Ca²⁺ and Mg²⁺ may be used, suchas NaOH, KOH and other monovalent alkali metals alone and/or in thepresence of metal salts such as CaCl₂ and MgSO₄, among others, as wellas reaction products of CaO and H₂O to yield Ca(OH)₂ and the reactionproducts of MgO and H₂O to yield Mg(OH)₂. Thus, for example, this excessof Ca(OH)₂ and/or Mg(OH)₂ can act as a reactant and interact with thebinder or reactant in-situ to form a Ca- and/or Mg-fatty acid saltencapsulate. In some embodiments, the use of excess free alkali andexcess binder or reactant can result in the formation of a fatty acidsalt coating on the compacted control release formulation of the presentinvention. In general, any known binder or reactant can be used in thepractice of this invention. Typically, the reactant or binder is a freefatty acid or a carboxylate salt-forming C₄-C₂₄ fatty acids. Fatty acidsuseful for the practice of this invention include, but are not limitedto, palm fatty acid distillate (PFAD), the individual or combinationfatty acids found therein such as, palmitic acid, stearic acid, oleicacid, linoleic acid, and the like, and/or other fatty acid-containingmixtures. Such mixtures may comprise, but are not limited to, non-freefatty acid ether extractable fats and other materials, such as themono-, di- and tri-gylceride forms of said groups. A free fatty acidcontent of from about 0.5% by weight to about 20% by weight of the corecompacted particle can be used, and can include non-free fatty acidether extractable fats and other materials. In yet another embodiment,the free fatty acid content can be from about 0.5% by weight to about10% by weight of the core compacted particle, and can include non-freefatty acid ether extractable fats and other materials.

A volume of core particles as described can be compacted into pellets byconventional means such as extrusion. Any known pelletizer can be used,for example, any known pellet mill. The core particles are pressed intopellets by extrusion through a die. In the invention process elaboratedabove, either of the coatings can be the first applied to the pellets,or pre-mixed before application. As an optional step, the pellets thencan be encapsulated with a final outer coating of wax or polymericmaterial to form a further semi-permeable barrier to a ruminal fluid.

The following Examples are further illustrative of the presentinvention. The components and specific ingredients are presented asbeing typical, and various modifications can be derived in view of theforegoing disclosure within the scope of the invention.

Example I

Calcium salt of palm fatty acid distillate flakes with Ca(OH)₂(Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA) andL-lysine*HCl powder (as specified in Table 1) were batched and blended.The Megalac® used had a fat (petroleum ether extract) %, free fatty acid% (based on palmitic) and Ca(OH)₂% of ca. 5%, ca. 0.2% and ca. 2%,respectively. After mixing, the feed was fed to a CPM Master Model 1000pellet mill via an auger feeder-conditioning chamber and pelletized. Theresultant pellets were screened to remove fines and cooled via an airblower. Solubility leaching and in-sacco bag study leaching were used togauge the control release of L-lysine from Megalac®-L-lysine*HCl-basedpellets (see Table 1); if the Megalac®-L-lysine*HCl-based pellet iseffective at mitigating the loss of the L-lysine from the pellet, thenelevated L-lysine concentrations in the resultant pellets will result ascompared to the non-pelleted blend, thus demonstrating the controlrelease properties of the pellets. While it is desirable for enhancingrumen bypass L-lysine in this example, the control release formulationin terms of fatty acid reactant type and levels, hydroxide and/orcarbonate of an alkali metal type and levels and the compactionextrusion process, among other factors, can be tailored accordingly tocontrol, for example, fatty acid salt formation (degree of reaction),degree of compaction of the resultant extruded pellet, cohesiveness ofthe pellet, among other physical and chemical properties, which dictatethe control release characteristics of the core materials.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 1 (Table 1)=15%.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 1 (Table 1)=21%.

Experiment 1 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults.

Example II

Calcium salt of palm fatty acid distillate flakes with Ca(OH)₂(Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA), L-lysine*HClpowder and additive (as specified in Table 1) were batched and blended.The Megalac® used had a fat (petroleum ether extract) %, free fatty acid% (based on palmitic) and Ca(OH)₂% of ca. 5%, ca. 0.2% and ca. 2%,respectively. Liquid stearic acid (Acros Organics N.V., Fair Lawn, N.J.)was then added to the dry blend and blended for 2 minutes. The stearicacid used had a fat (petroleum ether extract) % and free fatty acid % ofca. 100% and ca. 100%, respectively. After mixing, the feed was fed to aCPM CL-3 pellet mill via an auger feeder and pelletized. The resultantpellets were screened to remove fines and cooled via an air blower.Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine fromMegalac®-L-lysine*HCl-additive-based pellets (see Table 1); if theMegalac®-L-lysine*HCl-additive-based pellet is effective at mitigatingthe loss of the L-lysine from the pellet, then elevated L-lysineconcentrations in the resultant pellets will result as compared to thenon-pelleted blend, thus demonstrating the control release properties ofthe pellets. While it is desirable for enhancing rumen bypass L-lysinein this example, the control release formulation in terms of fatty acidreactant type and levels, hydroxide and/or carbonate of an alkali metaltype and levels and the compaction extrusion process, among otherfactors, can be tailored accordingly to control, for example, fatty acidsalt formation (degree of reaction), degree of compaction of theresultant extruded pellet, cohesiveness of the pellet, among otherphysical and chemical properties, which dictate the control releasecharacteristics of the core materials.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 2 (Table 1)=38%.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 2 (Table 1)=46%.

Experiment 2 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults.

Example III

Calcium salt of palm fatty acid distillate flakes with Ca(OH)₂(Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA), L-lysine*HClpowder/granules and additive (as specified in Table 1) were batched andblended. The Megalac® used had a fat (petroleum ether extract) %, freefatty acid % (based on palmitic) and Ca(OH)₂% of ca. 5%, ca. 0.2% andca. 2%, respectively. Palm fatty acid distillate (PFAD) liquid (PT BukitKapur Reksa, Indonesia) was then added to the dry blend and blended for2 minutes. The PFAD used had a fat (petroleum ether extract) % and freefatty acid % of ca. 100% and ca. 81% (based on palmitic), respectively.After mixing, the feed was fed to a CPM CL-3 pellet mill via an augerfeeder and pelletized. The resultant pellets were screened to removefines and cooled via an air blower. Solubility leaching and in-sacco bagstudy leaching were used to gauge the control release of L-lysine fromMegalac®-L-lysine*HCl-additive-based pellets (see Table 1); if theMegalac®-L-lysine*HCl-additive-based pellet is effective at mitigatingthe loss of the L-lysine from the pellet, then elevated L-lysineconcentrations in the resultant pellets will result as compared to thenon-pelleted blend, thus demonstrating the control release properties ofthe pellets. While it is desirable for enhancing rumen bypass L-lysinein this example, the control release formulation in terms of fatty acidreactant type and levels, hydroxide and/or carbonate of an alkali metaltype and levels and the compaction extrusion process, among otherfactors, can be tailored accordingly to control, for example, fatty acidsalt formation (degree of reaction), degree of compaction of theresultant extruded pellet, cohesiveness of the pellet, among otherphysical and chemical properties, which dictate the control releasecharacteristics of the core materials.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 3 (Table 1)=29%.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 3 (Table 1)=43%.

Experiment 3 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults.

Example IV

Calcium stearate flakes (Baerlocher USA, Cincinnati, Ohio), L-lysine*HClgranules and additive (as specified in Table 1) were batched andblended. The calcium stearate used had a fat (petroleum ether extract)%, free fatty acid % and Ca(OH)₂% of ca. 0.3%, ca. 0.3% and ca. 0.1%,respectively. Liquid stearic acid (Acros Organics N.V., Fair Lawn, N.J.)was then added to the dry blend and blended for 2 minutes. The stearicacid used had a fat (petroleum ether extract) % and free fatty acid % ofca. 100% and ca. 100%, respectively. After mixing, the feed was fed to aCPM CL-3 pellet mill via an auger feeder and pelletized. The resultantpellets were screened to remove fines and cooled via an air blower.Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine fromCa-stearate-L-lysine*HCl-additive-based pellets (see Table 1); if theCa-stearate-L-lysine*HCl-additive-based pellet is effective atmitigating the loss of the L-lysine from the pellet, then elevatedL-lysine concentrations in the resultant pellets will result as comparedto the non-pelleted blend, thus demonstrating the control releaseproperties of the pellets. While it is desirable for enhancing rumenbypass L-lysine in this example, the control release formulation interms of fatty acid reactant type and levels, hydroxide and/or carbonateof an alkali metal type and levels and the compaction extrusion process,among other factors, can be tailored accordingly to control, forexample, fatty acid salt formation (degree of reaction), degree ofcompaction of the resultant extruded pellet, cohesiveness of the pellet,among other physical and chemical properties, which dictate the controlrelease characteristics of the core materials.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 4 (Table 1)=4%.

In-sacco Bypass (ISB). Not completed due to the low solubility leachingresult.

Experiment 4 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults.

Example V

Calcium salt of palm fatty acid distillate flakes with Ca(OH)₂(Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA), L-lysine*HClpowder/granules and additive (as specified in Table 1) were batched andblended. The Megalac® used had a fat (petroleum ether extract) %, freefatty acid % (based on palmitic) and Ca(OH)₂% of ca. 5%, ca. 0.2% andca. 2%, respectively. Liquid soy oil (Spectrum Organic Products, LLC,Petaluma, Calif.) was then added to the dry blend and blended for 2minutes. The soy oil used had a fat (petroleum ether extract) % and freefatty acid % of ca. 100% and ca. 0.5%, respectively. After mixing, thefeed was fed to a CPM CL-3 pellet mill via an auger feeder andpelletized. The resultant pellets were screened to remove fines andcooled via an air blower. Solubility leaching and in-sacco bag studyleaching were used to gauge the control release of L-lysine fromMegalac®-L-lysine*HCl-additive-based pellets (see Table 1); if theMegalac®-L-lysine*HCl-additive-based pellet is effective at mitigatingthe loss of the L-lysine from the pellet, then elevated L-lysineconcentrations in the resultant pellets will result as compared to thenon-pelleted blend, thus demonstrating the control release properties ofthe pellets. While it is desirable for enhancing rumen bypass L-lysinein this example, the control release formulation in terms of fatty acidreactant type and levels, hydroxide and/or carbonate of an alkali metaltype and levels and the compaction extrusion process, among otherfactors, can be tailored accordingly to control, for example, fatty acidsalt formation (degree of reaction), degree of compaction of theresultant extruded pellet, cohesiveness of the pellet, among otherphysical and chemical properties, which dictate the control releasecharacteristics of the core materials.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 5 (Table 1)=9%.

In-sacco Bypass (ISB). Not completed due to the low solubility leachingresult.

Experiment 5 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults.

Example VI

Calcium salt of palm fatty acid distillate flakes with Ca(OH)₂(Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA), L-lysine*HClpowder/granules and liquid PFAD additive (as specified in Table 1) werebatched and blended. The Megalac® used had a fat (petroleum etherextract) %, free fatty acid % (based on palmitic) and Ca(OH)₂% of ca.5%, ca. 0.2% and ca. 2%, respectively. The PFAD (PT Bukit Kapur Reksa,Indonesia) used had a fat (petroleum ether extract) % and free fattyacid % of ca. 100% and ca. 81% (based on palmitic), respectively. Theresultant mash was not pelletized.

Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine fromMegalac®-L-lysine*HCl-additive-based mash (see Table 1).

Characterization—Solubility Leaching. The mash was exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the mash was removed, collected on a filterpaper, washed with water and then dried. Mash “before exposure” and“after exposure” were analyzed for N-content (Dumas combustion method)and the % bypass (% remaining)/Solubility Index Factor (SIF), wascalculated as follows: SIF=[(Combustion N % “afterexposure”)/(Combustion N % “before exposure”)]×[(Weight of mash “afterexposure”)]/(Weight of mash “before exposure”)]×100. SIF for Experiment6 (Table 1)<1%.

In-sacco Bypass (ISB). Not completed due to the low solubility leachingresult.

Experiment 6 of Table 1 includes some additional formulation details,processing details, experimental details and efficacy/characterizationresults. Experiment 6 serves as a representative example for thenon-pelleted forms of the formulations described herein.

TABLE 1 Pellet and mash formulation details, efficacy andcharacterization results. % Bypass End % Bypass (In-sacco Liquid FeedPellet (In-house Bypass Ca-fatty Free L-lysine*HCl Reactant Temp. Temp.leaching, ISB Experiment Die Size L/D acid, % Ca(OH)₂ % Additive, %Compacted (F.) (F.) SIF (24 h)) (12 h)) 1 5/32″ × 7.3 Megalac ®, Yes 20None Yes, Pellet 100 125 15 21 ⅞″ 80 2 3/16″ × 5.3 Megalac ®, Yes 20Stearic Yes, Pellet 140 130 38 46 1″ 77 Acid, 3 3 3/16″ × 8.0 Megalac ®,Yes 20 PFAD, 3 Yes, Pellet 125 160 29 43 1½″ 77 4 3/16″ × 5.3 Calcium No20 Stearic Yes, Pellet 125 112 4 x 1″ Stearate, 77 Acid, 3 5 3/16″ × 8.0Megalac ®, Yes 20 Soy Oil, 3 Yes, Pellet 130 147 9 x 1½″ 77 6 NA NAMegalac ®, Yes 20 PFAD, 3 No, Mash 100 NA <1 x 77

Example VII

Pellet preparation. Calcium salt of palm fatty acid distillate flakeswith Ca(OH)₂ (Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA),L-lysine*HCl granules and additive (as specified in Table 2) werebatched and blended. The Megalac® used had a fat (petroleum etherextract) %, free fatty acid % (based on palmitic) and Ca(OH)₂% of ca.5%, ca. 0.2% and ca. 2%, respectively. Liquid stearic acid (AcrosOrganics N.V., Fair Lawn, N.J.) was then added to the dry blend andblended for 2 minutes. The stearic acid used had a fat (petroleum etherextract) % and free fatty acid % of ca. 100% and ca. 100%, respectively.After mixing, the feed was fed to a CPM CL-3 pellet mill via an augerfeeder and pelletized. The resultant pellets were screened to removefines and cooled via an air blower.

Coating preparation. Stearic acid coating. A stearic acid liquid at ca.220° F. was spray applied onto the abovementioned pellets (ca. 100° F.)as they tumbled in a candy coater until an ca. 10% (by weight) coatingwas applied.

Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine from the uncoatedMegalac®-L-lysine*HCl-additive-based pellets and the stearic acid-coatedpellets (see Table 2); if the stearic acid coating is effective atmitigating the loss of the L-lysine from the pellet, then elevatedL-lysine concentrations in the resultant pellets will result as comparedto the uncoated pellet.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 7 and Experiment 8 (Table2)=28% and 40%, respectively.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 7 and Experiment 8(Table 2)=55% and 66%, respectively.

Experiment 7 and Experiment 8 of Table 2 include some additionalformulation details, processing details, experimental details andefficacy/characterization results.

Example VIII

Pellet preparation. Calcium salt of palm fatty acid distillate flakeswith Ca(OH)₂ (Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA),L-lysine*HCl granules and additive (as specified in Table 2) werebatched and blended. The Megalac® used had a fat (petroleum etherextract) %, free fatty acid % (based on palmitic) and Ca(OH)₂% of ca.5%, ca. 0.2% and ca. 2%, respectively. Palm fatty acid distillate (PFAD)liquid was then added to the dry blend and mixed for 2 minutes. The PFAD(PT Bukit Kapur Reksa, Indonesia) used had a fat (petroleum etherextract) % and free fatty acid % of ca. 100% and ca. 81% (based onpalmitic), respectively. After mixing, the feed was fed to a CPM CL-3pellet mill via an auger feeder and pelletized. The resultant pelletswere screened to remove fines and cooled via an air blower.

Calcium fatty acid coatings—Method 1. A calcium fatty acid salt slurrywas prepared using palm fatty acid distillate and Ca(OH)₂. Palm fattyacid distillate (ca. 88% by weight) at ca. 200° F. was added to Ca(OH)₂(ca. 12% by weight) at ca. 80° F. and mixed for ca. 1 minute. Theresultant slurry that consisted of newly formed calcium fatty acid salt,palm fatty acid distillate and Ca(OH)₂ was then applied onto ca. 70° F.pellets as the pellets tumbled in a drum coater at ca. 38 RPM. Anadditional charge of Ca(OH)₂ was then added to the pellets to completethe calcium fatty acid salt reaction and to separate the pellets. Thepellets were tumbled for several minutes until the pellets cooled toabout ambient temperature.

Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine from the uncoatedMegalac®-L-lysine*HCl-additive-based pellets and the Ca-fatty acidsalt-coated (Method 1) pellets (see Table 2); if the Ca-fatty acid saltcoating (Method 1) is effective at mitigating the loss of the L-lysinefrom the pellet, then elevated L-lysine concentrations in the resultantpellets will result as compared to the uncoated pellet.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 9 and Experiment 10 (Table2)=46% and 48%, respectively.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 9 and Experiment 10(Table 2)=61% and 77%, respectively.

Experiment 9 and Experiment 10 of Table 2 include some additionalformulation details, processing details, experimental details andefficacy/characterization results.

Example IX

Pellet preparation. Calcium salt of palm fatty acid distillate flakeswith Ca(OH)₂ (Megalac®, Church & Dwight Co., Inc., Princeton, N.J. USA),L-lysine*HCl powder/granules and additive (as specified in Table 2) werebatched and blended. The Megalac® used had a fat (petroleum etherextract) %, free fatty acid % (based on palmitic) and Ca(OH)₂% of ca.5%, ca. 0.2% and ca. 2%, respectively. Liquid palm fatty acid distillate(PFAD) liquid was then added to the dry blend and mixed for 2 minutes.The PFAD (PT Bukit Kapur Reksa, Indonesia) used had a fat (petroleumether extract) % and free fatty acid % of ca. 100% and ca. 81% (based onpalmitic), respectively. After mixing, the feed was fed to a CPM CL-3pellet mill via an auger feeder and pelletized. The resultant pelletswere screened to remove fines and cooled via an air blower.

Calcium fatty acid coatings—Method 2. A solution containing ca. 50%calcium fatty acid salt and ca. 50% palm fatty acid distillate (PFAD)was prepared; calcium fatty acid salt granules (ca. 80° F.) were addedto liquid palm fatty acid distillate (ca. 240° F.) and stirred until thecalcium fatty acid salt was solubilized in the palm fatty aciddistillate. The resultant solution at ca. 240° F. was then spray-applied(ca. 80 psig) onto ca. 80° F. pellets as they tumbled in a drum coaterat ca. 38 RPM. Calcium fatty acid salt powder that contained Ca(OH)₂ wasperiodically applied to the pellets to complete the fatty acid saltreaction and to separate the pellets. The pellets were tumbled forseveral minutes until the pellets cooled to about ambient temperature.

Solubility leaching and in-sacco bag study leaching were used to gaugethe control release of L-lysine from the uncoatedMegalac®-L-lysine*HCl-additive-based pellets and the Ca-fatty acidsalt-coated (Method 2) pellets (see Table 2); if the Ca-fatty acid saltcoating (Method 2) is effective at mitigating the loss of the L-lysinefrom the pellet, then elevated L-lysine concentrations in the resultantpellets will result as compared to the uncoated pellet.

Characterization—Solubility Leaching. The pellets were exposed to aphosphate buffer solution (ca. 0.2 M) at pH ca. 6.7 and at ca. 35° C.with subtle shaking. At 24 h the pellets were removed, washed with waterand then dried. Pellets “before exposure” and “after exposure” wereanalyzed for N-content (Dumas combustion method) and the % bypass (%remaining)/Solubility Index Factor (SIF), was calculated as follows:SIF=[(Combustion N % “after exposure”)/(Combustion N % “beforeexposure”)]×[(Weight of pellets “after exposure”)]/(Weight of pellets“before exposure”)]×100. SIF for Experiment 11 and Experiment 12 (Table2)=29% and 47%, respectively.

In-sacco Bypass (ISB). Pellets housed in nylon bags were placed in thecow's rumen and exposed to the rumen fluid for 12 h. At 12 h, thepellets were removed from the rumen, rinsed with water and then dried.Pellets “before exposure” and “after exposure” were analyzed forN-content (Kjeldahl method) and the % bypass (% remaining)/In-saccoBypass (ISB), was calculated as follows: ISB=[(N % “after exposure”)/(N% “before exposure”)]×[(Weight of pellets “after exposure”)]/(Weight ofpellets “before exposure”)]×100. ISB for Experiment 11 and Experiment 12(Table 2)=43% and 72%, respectively.

Experiment 11 and Experiment 12 of Table 2 include some additionalformulation details, processing details, experimental details andefficacy/characterization results.

TABLE 2 Pellet and coating experimental details andefficacy/characterization results. % Uncoated End Bypass % Bypass Pelletor Liquid Feed Pellet (In-house (In-sacco Coated Ca-fatty L- ReactantsTemp. Temp. Coating leaching, Bypass, Experiment Pellet acid, %lysine*HCl % Additive, % Die Size L/D (F) (F) Details SIF (24 h)) ISB(12 h)) 7 Uncoated 77 20 Stearic Acid, 3 3/16″ × 5.3 140 131 None 28 55Pellet 1″ 8 Coated “7” Coated 40 66 Pellet with ca. 10% stearic acid 9Uncoated 77 20 PFAD, 3 3/16″ × 8.0 120 147 None 46 61 Pellet 1½″ 10Coated “9” Coated 48 77 Pellet with ca. 10% Ca- fatty acid (Method 1) 11Uncoated 77 20 PFAD, 3 3/16″ × 8.0 125 160 None 29 43 Pellet 1½″ 12Coated “11” Coated 47 72 Pellet with ca. 10% Ca- fatty acid (Method 2)

1. A control release formulation in compacted form comprising: (a) afatty acid salt, (b) one or more biologically active agents, (c) a freealkali and (d) a binder.
 2. The control release formulation of claim 1wherein said formulation is compacted and extruded into pellets.
 3. Thecontrol release formulation of claim 1 wherein said fatty acid salt is aC₄-C₂₄ fatty acids salt.
 4. The control release formulation of claim 1wherein said one or more biologically active agents are selected fromthe group consisting of amino acids, vitamins, minerals, trace elements,enzymes, proteins, non-protein nitrogen compounds, and medicaments. 5.The control release formulation of claim 1 wherein said free alkali is ahydroxide and/or carbonate of an alkali metal or alkaline earth metal.6. The control release formulation of claim 5 wherein said free alkaliis Ca(OH)₂ and/or Mg(OH)₂.
 7. The control release formulation of claim 1wherein a reaction product is formed in situ between said free alkaliand said binder.
 8. The control release formulation of claim 1 whereinsaid binder is a carboxylate salt-forming C₄-C₂₄ fatty acids.
 9. Thecontrol release formulation of claim 3 wherein said fatty acid salt isderived from palm fatty acid distillate, the individual or combinationfatty acids found therein, and/or other fatty acid-containing mixtures.10. The control release formulation of claim 4 wherein said formulationcomprises a single biologically active agent, and wherein saidbiologically active agent is lysine.
 11. The control release formulationof claim 8 wherein said binder is selected from the group consisting ofpalm fatty acid distillate, the individual or combination fatty acidsfound in palm fatty acid distillate, stearic acid, palmitic acid, oleicacid, linoleic acid, non-free fatty acid ether extractable fats, themono-, di- and tri-gylceride forms of non-free fatty acid etherextractable fats, and mixtures thereof.
 12. The control releaseformulation of claim 1 wherein said fatty acid salt comprises from about25 to about 99 weight percent of said formulation.
 13. The controlrelease formulation of claim 1 wherein said one or more biologicallyactive agents comprises from about 1 to about 75 weight percent of saidformulation.
 14. The control release formulation of claim 1 wherein saidfree alkali comprises from about 0.2 to about 10 weight percent of thetotal weight of the fatty acid salt.
 15. The control release formulationof claim 1 wherein said binder comprises from about 0.5 to about 20weight percent of said formulation.
 16. A rumen-bypass dietarysupplement comprising: (a) a fatty acid salt, (b) one or morebiologically active agents, (c) a free alkali metal salt and/or alkalineearth metal salt and (d) a binder; wherein said dietary supplementimproves the lactational performance of dairy cattle.
 17. A process forproducing a control release formulation comprising: compacting intopellets a control release formulation comprising: (a) a fatty acid salt,(b) one or more biologically active agents, (c) a free alkali, and (d) abinder.
 18. The process of claim 17, said process comprising the stepsof: (1) blending a particulate of C₄-C₂₄ fatty acid calcium and/ormagnesium salts containing a free alkali with one or more biologicallyactive agents and a binder; and (2) compacting and extruding saidformulation into pellets.
 19. The process of claim 18 wherein saidbinder reacts in situ with said free alkali present with saidparticulate of C₄-C₂₄ fatty acid calcium and/or magnesium salts.
 20. Theprocess of claim 18 wherein said one or more biologically active agentsare selected from the group consisting of amino acids, vitamins,minerals, trace elements, enzymes, proteins, non-protein nitrogencompounds, and medicaments.
 21. The process of claim 18 wherein saidfree alkali is a hydroxide and/or carbonate of an alkali salt and/oralkaline earth metal.
 22. The process of claim 18 wherein said freealkali is Ca(OH)₂ or Mg(OH)₂.
 23. The process of claim 18 wherein saidbinder is a carboxylate salt-forming C₄-C₂₄ fatty acids.
 24. The processof claim 17 wherein said free alkali is present from about 0.2 to about10 weight percent of said particulate of C₄-C₂₄ fatty acid calciumand/or magnesium salts.
 25. The process of claim 23 wherein said freefatty acid binder is selected from the group consisting of palm fattyacid distillate, stearic acid, palmitic acid, oleic acid and linoleicacid.
 26. The process in accordance with claim 20 wherein said one ormore biologically active agents comprises one or more amino acidsselected from the group consisting of alanine, glycine, lysine,methionine, methionine hydroxy analog, tryptophan, arginine, threonine,valine, leucine, isoleucine, histidine, phenylalanine, glutamine andglutamic acid.